Education

Postdoctoral Fellow, Strasbourg, FrancePh.D. University of MassachusettsB.A. Bowdoin College

Director of Medical Careers Advising Program

As Director of Clark’s Medical Careers Advising Program and Chair of the Premedical and Predental Advisory Committee, Dr. Thurlow advises students interested in health related professions including medical doctors (MD, DO), dentistry, optometry, podiatry, veterinary medicine, physician assistant, nurse practioner, physical therapy, occupational therapy, public health, and many others. Many new features of our program help students find their own “right path” into medicine and assist the Premedical and Predental Advisory Committee in preparing personalized letters of recommendation for Clark students applying to medical and dental schools.

Prior Research

Adding "CCA" to tRNAsFor nearly 20 years, our group investigated the molecular basis underlying interactions between transfer RNA (tRNA) and the processing enzyme ATP,CTP:tRNA nucleotidyltransferase ("NT"). NT catalyzes joining of CMP and AMP onto the 3'end of tRNA molecules that lack all or part of the universally conserved sequence CCA. We are trying to understand how this enzyme adds only the CCA sequence without using a nucleic acid template.

Projects included:

Chemical modification experiments identified bases essential for interaction with NT that are located at the “corner” of a tRNA’s three dimensional structure, where the T- and D-loops come together. These results suggested a model in which NT interacts along the “top” of a tRNA, with one end binding to the tRNA’s corner and the other end binding the nucleotide substrates and adding them to the 3’end of the tRNA.

Mini RNA helices, structural analogs of the “top” of a tRNA, were shown to be effective substrates for NT – thereby confirming our model for the interaction based on chemical modification experiments.

Site-directed mutagenesis of NT genes created enzymes with altered amino acid sequences, or large deletions. The mutants, as anticipated, exhibited decreased enzymatic activity – some because they reduced the ability of the tRNA to bind and some because they reduced binding of the nucleotides.

Computer modeling of interactions between NT and its substrates ATP, CTP, and tRNA revealed possible differences among the many ways in which ATP and CTP could bind.

Hypothetical model for NT interacting with the top of a tRNA (left), based on chemical modification experiments - sketched by Fred LaRivere’94, while working in our lab as an undergraduate in 1993, compared to crystal structure (right) published over ten years later (Xiong and Steitz (2004), Nature 430:640):

Computer-based predicted model for the catalytic region of a Class I NT constructed by our group (Megan Albert '02) in collaboration with a lab in Poland (Janusz Bujnicki) (left), just prior to the publishing of the first crystal structure of a Class I NT (right; by Okabe et al. (2003) EMBO J. 22:5918-5927).

Selected Publications

De la Torre, D., Ritter, H., Thurlow, D.L., and Voce, K. (2012) Challenges faced by community college pre-health students and their advisors. The Advisor 32(2): 24-31.

D.L. Thurlow, G.M. *Pulido and K.J. *Millar (1997). "Unidentified open reading frames in the genome of Methanococcus jannaschii are similar in sequence to an archaebacterial gene for tRNA nucleotidyltransferase." Journal of Molecular Evolution, 44: 686-689.